← The Fellow on Call: The Heme/Onc Podcast
The Fellow on Call: The Heme/Onc Podcast
Episode 147: Myeloma Series, Pt. 7 - Transplant Consolidation for Multiple Myeloma (2026)
Ronak Mistry, Vivek Patel, Dan Hausrath
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Hey, friends. This episode of the Fellow on Call is not meant to be used for medical advice and is intended for educational purposes only. Patient information has been modified to ensure privacy. The views expressed in this episode do not necessarily reflect the views of our employers.
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Enjoy the best Oncologists never stop asking questions on premium. Fellows can do the same. Connect with over 100 experts and get real one on one answers in hours. Free to join at primum Co. That's P R I M u m co.
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A
Welcome to another episode of the Fellow on Call, the Hemong Podcast. We're coming at you from Rouleau University Medical Center. I'm Ronuk.
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B
I'm Vivek.
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C
And I'm Sean.
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A
And in today's episode, we continue on our myeloma journey, this time continuing to talk about how we manage our patients and focusing specifically on transplant consolidation for patients with myeloma.
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B
Excited to get into this one. We're really going to breeze through some of the key updates in this space, the trials that we have for transplant. This is obviously an evolving space, so just excited for our listeners to understand the data as it is going to change in the next several years.
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C
There's a lot of exciting updates that probably will be coming in the next few years, but I think it's important to understand the data of how we got to where we are right now because that really shapes the conversation about what we are looking at going forward on how to improve our care for myeloma.
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A
I'm stoked. Without further ado, let's roll that show, guys. I know we have a lot of really, really, really important things to talk about today, but I just want to share one of the proudest moments I think of my entire life at our gym. This month was a burpee over your partner challenge while your partner planks. And my wife decided that she wanted to be my partner. We won. We did 1,156 burpees and we did 656 of those today.
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B
So it's nice that Roanoke's proudest achievement, I mean, this guy, you know, is a physician, did all these other things and his proudest achievement is doing a bunch of burpees. I want to say this morning I had a bagel. It was a lox bagel. It was very good. Did not exercise. I should probably get my stuff together.
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C
I played tennis this morning. So I think somewhere probably in the middle between those two, it's all about balance.
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A
So we all sort of balance out each other's activities. But a bagel with lox sounds pretty good. Guys, I'm excited to continue this conversation on myeloma, this time focusing on transplant consolidation. And so let's just get things rolling and Vivek, do you want to kick us off with a case?
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B
Yeah. So we have a 55 year old previously healthy female with newly diagnosed standard risk IgG Kappa multiple myeloma. Check out our previous episodes. Check out the new IMWG guidelines on high risk multiple myeloma. Just to clarify, on cytogenetics, there was no amplification or gain 1q, no deletion, 1p deletion 17p translocation 414 or translocation 1416. So ultimately we had this standard risk multiple myeloma patient. She was treat with DARA VRD for four cycles per the Perseus trial and achieved a VGPR with a detectable M spike but no quantifiable M spike and a normal free light chain ratio. She had a bone marrow biopsy that showed a 5% population of plasma cells. So when she was originally diagnosed, she was referred to a transplant center. Shawn really talked about the importance of referring early for transplant, particularly if you're in the community and she's ready for this auto stem cell transplant. So we talked about the idea of high dose melphalan followed auto stem cell rescue in prior episodes. But really today we really need to talk about the nitty gritty behind this. You know, what is the data? What is the PFS benefit of doing this approach? And this will lay the groundwork for how things might change in the future. So remember to check out our show notes for more granular detail and we'll include some trials not discussed in today's episode for your reference. But we're going to go through three key trials today, evaluating transplant in the modern era, IFM 2009 determination, and the recently published Midus trial, because I think all of these are pretty informative to our current standards of care. So, Sean, can you kick us off a little bit by talking to us about the IFM 2009 trial?
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C
Yeah. So the IFM 2009 trial. So this was a trial where all the patients that were involved in this trial got induction with RVD for three cycles. They were then randomized to transplant, followed by two cycles of RVD versus getting no transplant and doing five cycles of RVD as their consolidation instead. All of these patients then went on to do revlimid maintenance for one year. And it's important to note that all patients had their stem cells collected, regardless of what the randomization was. So even if they ended up not going for transplant initially, they still had their stem cells collected up front. The primary endpoint for this study was progression free survival. And there were a total of 700 patients in this study. This study showed that there is a PFS benefit but not an overall survival benefit. So the eight year progression free survival was 35% with transplant versus 23% in the patients that did not do transplant upfront. Eight year overall survival was about 60% in both groups. 77% of the patients that did not receive transplant upfront did go on to get a transplant at their relapse and they had a better PFS2 than the early transplant group, which makes sense because they were able to go on and do this intensive transplant treatment at the time of the relapse. And so really the key takeaways from this trial is that this is a trial looking at almost early versus delayed transplant and showed that there was a progression free survival benefit for PFS1 but not an overall survival benefit. 35% of the patients at the eight year follow up were still in remission and off treatment. And so that's essentially six years of not getting any treatment. So remember that in the IFM study patients only got one year of maintenance revlimid after they did their consolidation, whether that included transplant or not. And that's 10% higher in the group who did not get the upfront transplant.
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B
I think this, this trial brings up a lot of important points here, is that early versus delayed transplant. This is one trial that shows us if you delay the transplant, you're not going to have a detriment in overall survival. That being said, some patients, when you think about this, it's like, well, why am I just going to be sitting here like a ticking time bomb? You know, I just want to get the transplant now. I'm younger, I'm fitter, I've already got this cancer diagnosis. Let put this behind me and knowing that I could potentially maximize some progression free survival benefit there. The other interesting thing here is there was one year of maintenance. So let's remember these numbers as we think about this, that the eight year PFS was again, we're looking at about 35% in some of these patients and I think that's a really important number to remember. So about a third of patients at 8 years enjoyed their progression free survival. And we're going to compare this as we look at our next trial, the determination trial. So Rene, can you talk about the determination trial?
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A
Yeah, so it was the same essentially the Same treatment paradigm as IFM 2009, except instead of Revlimid maintenance being stopped at one year, it was continued until disease progression. And the key thing to note is that fewer patients got transplant at relapse. So in this study three cycles of VRD was administered and then patients were randomized to transplant, followed by two cycles of VRD versus no transplant and five more cycles of vrd. And then they were continued on maintenance until disease progression. The primary endpoint here was progression free survival and Overall they included 873 patients of which 20% were considered high risk. The median progression free survival was 67 months versus 46 months. And this was notably approximately 20 months longer in both arms compared to the IFM 2009 trial that Sean just mentioned, suggesting that continuous revlimid maintenance improves outcomes over one year of fixed duration maintenance. So that's kind of a big deal. The big caveat is that cross trial comparisons have significant limitations, but this does inform our standard of care for revlimid maintenance until progression. Overall, there was no difference in overall survival despite a PFS benefit. Interestingly, with median of over 6 years of follow up, only a little over a quarter of patients. So roughly 28% got transplant at relapse in the no transplant arm. And this shows the great efficacy of novel agents and really puts into question the need for early transplant for all patients. There also was MRD negativity that was assessed in this and that was assessed by ngs to the 10 to the minus 5. Those who are MRD negative had better progression free survival and overall survival regardless of their treatment arm. MRD negativity was approximately 50% higher in the transplant group at the start of maintenance and there was 54% in the transplant group versus 40% in the no transplant group. Also potentially highlighting the opportunity to be using MRD negativity as a way to better understand what patients may benefit from transplant versus not.
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B
I think this is also another important thing here. So we have two critical trials. Again, this is without quadruple induction, so things are gonna get more complicated. We don't know what to do now that we have quadruple induction. Truly do we need to transplant all patients? Could we use MRD assessments to not transplant patients? Is or do we use the transplant to deepen our MRD negativity to get patients off of maintenance earlier? And these are the challenging questions that we just don't have answers to. I really want to talk about why PFS1 might matter and what the argument for early transplant is. If there's no overall survival benefit. Somebody could look at this and say why are you making somebody go through this crazy transplant process, super high doses of melphalan, messing up their lives, you know, stem cell rescue, it's a big deal for patients. Why do that if they're not going to live any longer? So what's the argument here? We know that each subsequent relaps relapse in myeloma has a shorter pfs, likely due to selection of more resistant clones and clonal evolutions of that myeloma. Many people believe that there is an operational cure, quote unquote. And there's a lot actually talked about this just in the last couple of weeks about what is cure. Is it patients that are living at normalized life expectancy or is it patients where they're disease free survival meaning they're not dying of their disease and they're not on treatment? That's really an operational cure that you're not on treatment, that you're not going to die from your disease and that you're kind of reset back to the general population for the most part. And I think that's what the thought is here, that maybe we can have long term treatment, free remission by transplanting all of our patients early and using MRD negativity, sustained MRD negativity to stop our maintenance therapy. And you know, in the next episode we'll talk about more a little bit about maintenance and I think that'll highlight really where the field is headed.
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B
The other thing I think is really interesting about this is that if you don't transplant a patient, there's a subgroup of patients who don't need transplant later. Do all patients need transplant up front? So I think that's another key takeaway here. Paradigms move forward as we use things like the Master 2 trial that's coming up. We can better risk, stratify our patients to say maybe this patient needs transplant, maybe not. And I think that's where things are headed. And then we also have this question of CAR t that's going to be another very interesting thing as we move forward. But to continue on to this discussion, Sean, can you tell us a little bit about the Midus trial? Because I think that's also another key pivotal study that just came out earlier in 2025.
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C
So the Midus trial I think is definitely an important trial to understand both in terms of what it tells us and maybe some limitations in terms of how we might apply it to our practice today. So again, as we've sort of emphasized, the rate of development of new treatments is really outpacing our ability to design and conduct new trials to just because of how effective our medications are. So although we've talked a little bit about the data for transplant with both IFM and determination, we don't yet have a randomized trial that's specifically comparing transplant to no transplant with quadruplet anti CD38 regimens such as Dara VRD yet. So we're generally extrapolating for our recommendations here. We did recently get initial results from this Midas trial that Vivek mentioned and that was published in the New England Journal in 2025. The MIDAS trial used isatuximab, which is another anti CD38 agent, carfilzomib, lenalidomide and dexamethasone or Issa KRD. The design of this trial is a little bit complex, so we'll include a link to the schema in our show notes, but this is essentially an ongoing phase three randomized, open label, active, controlled, parallel group multicentered study that includes transplant eligible patients with newly diagnosed myeloma who were treated with six cycles of Issa KRD as their induction. After induction, the patients who were able to achieve MRD negativity at the 10 to the minus fifth level so 1 in 100,000 cells do not have myeloma. Patients who were able to achieve this depth of MRD negativity after induction with Issa KRD were randomized to one of two arms for consolidation. So half of these patients went to autotransplant followed by two more cycles of issacrd, while the other half of patients did no transplant. Instead, they received six more cycles of Issac ard. After consolidation was complete, MRD was rechecked in all these patients, but now at the more sensitive 10 to the minus 6th level. So looking out of a million cells in the bone marrow, are there any myeloma cells that are still there? Notably, there is no difference in MRD negativity between the Autotransplant arm that incorporated transplant and consolidation versus the groups that just did consolidation. With additional cycles of Issa krd, longer follow up is needed. But this sort of raises the question for do all patients need transplant after a quadruple induction if they're able to already get to a very deep level of MRD negativity with their induction regimen alone? So that's one of the most important questions that this brings up, although it doesn't necessarily fully answer that question for us due to some differences in how this trial is designed compared to how many of us do our induction in the current day.
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B
I think one interesting thing about this, they used krd. And we've talked about this before. We've had the randomized trial, the endurance trial, that randomized patients VRD to KRD induction. And this is an older trial, but really informative. There's no difference in outcomes. And everybody thought, well, Carfilzomib is better than the second line setting, probably because the patient's seen Velcade before, right? And there's been this buzz that maybe Carfilzomib is better than Velcade in the upfront setting. To Sean's point, okay, they're using Carfilzomib instead of Velcade. That's one interesting little quirk here. We're mainly using Daratumumab here in the United States for most of our patients. That's another little quirk here. I think what's really interesting to me, the myeloma community has accepted MRD negativity as a surrogate endpoint for drug approval. And so if we had. Imagine. I wanna flip this a little bit. Let's just pretend this is a brand new spanking new drug, right? A new monoclonal antibody, a new daratumumab. We had MRD negativity as our primary endpoint. And let's say hypothetically, this new drug was less toxic than our standard dara. Or what we would say is, well, this is the same MRD negativity rates. We should approve it. And so I think that's really interesting to me. I think longer follow up is needed. This just highlights the fact that this auto transplant, this really intensive auto transplant, did not improve MRD negativity rates compared to consolidation. Here's the catch. It's sustained MRD negativity that matters. So anybody listening to this podcast, one time, point of MRD negativity, it ain't the whole story. It's sustained MRD negativity. And that's gonna be the key. So if we see this MRD negativity sustained at two years, three years, then we can say actually, do we need the transplant? And I think that's how the long term follow up of the Midus trial is really going to help us, these patients sustain their MRD negativity. I think that's going to be very interesting. And Sean, can you tell us a little bit more about other trials in this space that are ongoing right now?
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Yeah. So this same idea of can you take patients and use MRD as a way to stratify kind of what their risk is and also use that potentially to help make decisions about what you are doing, both for the consolidation and maintenance is a really, a really key idea. And I think it's going to be one of the main sort of paradigms that drives how we advance our care for myeloma going forward. So there are several trials that are currently underway. So trials such as Master 2, trials such as the faster trial, and these are trials are all looking at MRD as part of how they are evaluating patients. Looking at that idea of sustained MRD negativity. As Vivek said, one of the key things here is that we're starting to look at are there some patients, for example, who may be able to safely stop their maintenance medications and be able to just go back to close observation with continued surveillance at the MRD level, to looking at essentially what we call a treatment free MRD observation. I think that's gonna shape a lot of what our future induction regimens look like. Not only are they gonna be looking at transplant as well for consolidation, but there's likely going to be a lot of trials that are coming out in the next several years looking at alternatives such as, for example, using a bispecific antibody as part of their consolidation, or maybe using CAR T for consolidation. And so the role of transplant, I think in general, as we've kind of mentioned, we do think it provides benefit overall. But now we're trying to think about how can we be a little bit more selective about are there certain patients who maybe specifically benefit from transplant versus are there certain patients where maybe we've already gotten as deep as we really need to with their induction. And so maybe adding transplant for those patients really isn't doing too much to prolong how long they stay in remission.
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And that's so important, particularly when we think about secondary malignancies with a lot of alkylator exposure. That high dose mephalan ain't a chill thing. You're Also narrowing your stem cell pool, your stem cell reserve. We know a lot of the population has CHIP. Many populations with myeloma are above the age of 50, 60. So it's a very challenging thing. We don't want to cause a secondary leukemia, a secondary mds related to some of this therapy. So I these are going to be really important questions and thanks for walking us through that. I'm going to flip the case and Ronak, I'm going to ask you to summarize a little bit of the data here. So let's say actually this patient had a high risk multiple myeloma. They had a deletion 17p. And we've talked about this in the past. If you have high risk multiple myeloma, all these patients need to go to transplant in 2026. Right now we know all these patients need to go to transplant. And that's going to be a long time before that mantra changes. These high risk patients, we can get them into remission, but maintaining that remission is tough. And transplant is really, really, really important. In addition to maintenance, which we'll talk about in our next episode. Ronak, sometimes people talk about this idea of a tandem transplant here at the fellow on call. We don't really do tandem transplants. We don't agree with tandem transplants. Can you walk us through some of that weak data for tandem transplants by going through the stamina trial?
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Absolutely. So just a little bit of background. So the mantra in the history of oncology is generally that more is better. That's kind of what the theme has always been, although clearly we're trying to indicate that maybe that's changing. But in the mid-90s, the IFM group did a randomized trial looking at single versus double transplant and found benefit for double transplant, particularly for those who did not get VGPR or better after the first transplant. And this was done for patients who got vincristine, doxorubicin and dexamethasone induction. And they also got interferon maintenance. So unclear if it's necessary with the modern therapies that we use. And this sort of led to the development of the stamina trial that Vivek just mentioned. So the stamina trial specifically was done in the United States. They included patients who got two to 12 months of induction therapy, mainly with RVD and some with cyborg D. So again, different than the current landscape of how we're treating our patients, but important to still understand. All patients got transplant. And then we looked at, should we consolidate these patients with the second transplant or give them more RVD or do nothing. And everyone went on revlimid maintenance. They are randomized one to one to one and then. So the tandem transplant patients were followed by revlimid maintenance. The single transplant were followed by RVD times four for consolidation followed by revlimid maintenance. And then the single transplant was followed by revlimid maintenance without consolidation. And what they found was that there was no improvement in progression free survival or overall survival for the more intensive approaches compared to single transplant followed by revlimid maintenance. And so this is essentially our standard of care suggesting that more may not in fact be better. We could actually do less, deescalate the use of some of these toxic agents and continue these patients on maintenance therapy.
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B
And these results contrasted with a European study that we can link in our show notes as a historical study. And that study was complicated by it suggested tandem's transplant was superior and mainly driven by the high risk subgroup of patients. High risk in myeloma's definition has changed drastically over time. So this isn't the same high risk patients that we talk about today in 2026. There's several limitations that study, including the fact that everybody in that trial got cyborgy induction, not VRD or even a quad for four cycles. And we know that's inferior for particularly high risk patients. So I think the idea behind a tandem transplant for high risk patients, we just don't have enough data to support that in our modern era of therapy. And we think maintenance is more important in that category, which we'll talk about in our next episode. You know, it'd be nice in the future when have more of these trials with quads, you get better understanding of how the high risk patients respond to some of these therapies, then we can know what to do with the high risk patients. But the data is just very weak to support tandem transplant. I will note that in the Midus trial there was another randomization for MRD positive patients. So this trial that Sean had talked about that was if you're MRD positive, you either get single transplant versus double transplant, the tandem transplant, no difference in outcomes. So really to me there's very, very data for tandem transplant for these patients. So Sean can summarize everything we've talked about today, summarizing the, you know, we have this early versus delayed transplant, no OS benefit, the MIDAS trial, and then lastly, this idea of tandem transplant.
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A
Yeah.
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So I would say that overall the bottom line is that if you're taking care of a newly diagnosed patient for myeloma in 2026, when you get to consolidation for patients that are otherwise eligible for transplant, we still typically generally favor doing a consolidation autologous stem cell transplant and typically early on in patients, as it appears to provide a meaningful benefit in progression free survival, with a caveat that it does not appear to provide a benefit for overall survival at this point in time. And again, that may be largely related to the fact that we have so many more medications that are effective in later lines of therapy than we used to back in say, the early 2000s. We do have to recognize though that this recommendation for transplant is really extrapolated from earlier trials which did not include patients who were receiving anti CD 38 agents such as Daratumumab during their induction. So these were trials that involved VRD for induction. And so we do have to take that with a little bit of a grain of salt. But at the same time, it does represent at least the best randomized data that we have at the moment. The recent Midus trial that we mentioned may set the stage for us to help start reevaluating the role of transplant with more current treatment approaches, knowing that with these anti CD38 based induction regimens, we may be able to get patients into much deeper remissions than we were previously able to do. And as a result, the role of transplant may potentially be different, or at least we may potentially have a way to help select patients for the patients who may actually get a lot more benefit out of transplant versus those who may not necessarily benefit too much from it because they're already in a pretty deep remission. And so as we look forward to the future, we're really looking at different ongoing trials that are evaluating what we do in consolidation, and not just with transplant, but also comparing them to other advanced treatments such as bispecific T cell engagers as well as CAR T therapy, and using these potentially in lieu of transplant. So this may be one of the main areas that changes the most in the next several years. As these trials are completed and reported out, they may drastically reshape what we think about in terms of consolidation. But at least for right now, in 2026, in general, if you have a patient that is a good candidate for a transplant from a functional status standpoint and from a social support standpoint, then in general, we do still tend to recommend early autologous stem cell transplant.
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B
That was really, really well said, Sean. And I really want to highlight one thing through all of this, and Sean had mentioned this in our frontline myeloma episode refer to a transplant center early. Many of these transplant centers have clinical trials and that is so key for our patients with multiple myeloma right now. And these trials are well designed. It's like don't get a. That's huge. Maybe get CAR T. We're hopeful maybe that's going to cure these patients. Maybe it's going to look like what CAR T looked like in large B cell lymphoma. We just don't know. We've only used CAR T and we have a cell therapy episode coming up in patients who are fifth line or more in some cases and some cases for patients who are in the second line after on auto transplant and a triplet induction. So we'll talk about that in further details coming up. But that being said, that's the hope that we can operationally cure some of these patients. I think that's huge. Deescalate their maintenance. So always refer, even though we have this data that early versus delayed transplant, no OS benefit. What we're trying to do here is find the patients who will benefit, find the patients who won't. Now we have the tools to potentially do that. So really can't plug that enough. Anybody who's learning about this, listening about this, check out these trials, interpret them. But also remember, enrolling these patients on trial now is going to really pave the way for the future.
- [25:53]
A
So well done, guys. So well said. I think that wraps up another fantastic episode of the fellow on call. So until next time, we'll see you all later.
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B
See you later.
- [26:01]
C
See you later.